I do not agree with the authors that parenteral (injected) MTX equates to higher dose necessarily equates to higher toxicity. Dose for dose:
1) The gastrointestinal side-effects may be less with injection than through the oral route;
2) The parenteral route bypasses the First Pass Effect at the liver, with less insult on the liver compared to the oral route, and less destruction of the drug, thus making more MTX being available to the joints. For severe disease at presentation, I prefer to start with subcutaneous MTX 25mg/wk, then taper dose or switch to oral when disease comes under good control. I have not seen more intolerance or side-effects this way (touch wood).
Anecdotally, I find that patients only start complaining of nausea after their joint disease had come under good control. By then, I could taper or switch treatment with less risk of the disease flaring. Perhaps noticing the nausea is an indication that patients are feeling better and no longer overwhelmed by their joint pains! If I have to escalate an oral dose beyond 20mg weekly, either I separate into 2 doses 1 day apart, or I switch to the injected form. Separate studies have demonstrated that the oral absorption and bioavailability plateaus off above 15mg to 17.5mg as a single dose.
Here’s evidence that injected MTX is more effective and better tolerated in RA patients than the oral formulation. Its better efficacy may even negate the need for far more expensive biologics and small molecules in many patients.
Similar efficacy may be seen in other conditions like Psoriasis, Psoriatic Arthritis and Dermatomyositis; and should be explored before escalating to targeted therapies.
Methotrexate dosage as a source of bias in biological trials in rheumatoid arthritis: a systematic review.
The secret’s out. Is scaremongering of steroid and MTX “toxicities” the pharmas’ modus operandi?